Feedback modulation of glucose-induced insulin secretion by arachidonic acid metabolites: possible molecular mechanisms and relevance to diabetes mellitus.
Recent evidence suggests that glucose stimulation of insulin release may trigger a classic negative feedback loop involving local release of an inhibitor of beta cell function. One or more metabolite of arachidonic acid could comprise such putative system. Several metabolic events triggered by glucose-induced stimulus-secretion coupling (such as calcium influx, membrane turnover, augmented reduced pyridine nucleotide or glutathione levels, and alterations in toxic oxygen radical availability) would be expected to alter arachidonic acid release and subsequent metabolism via the lipoxygenase or cyclo-oxygenase pathways. At lease one arachidonate derivative (prostaglandin E) inhibits insulin secretion, and several inhibitors of prostaglandin synthesis augment glucose-induced insulin release in normal subjects and type II diabetics. Development of more selective inhibitors of arachidonate metabolism could represent a new approach to therapeutic manipulation of beta cell function.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D005246:Feedback; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000503:physiopathology; D008954:Models, Biological; D011453:Prostaglandins / Q000378:metabolism
D001095:Arachidonic Acids; D007328:Insulin; D011453:Prostaglandins; D016718:Arachidonic Acid; D005947:Glucose